Dermatology

Chagas Disease (American Trypanosomiasis)

Are You Confident of the Diagnosis?

Chagas disease can be divided into acute and chronic phases. The vector tends to feed on blood from the mucous membranes of the eye or the mouth. During feeding it defecates. Infection takes place by rubbing the insect feces that contain the trypomastigotes in to the wound or mucous membranes Figure 1).

Local inflammation can lead to swelling of the eyelids (Romaña’s sign, Figure 2) or the lips. Inflammation around the insect wounds at other sites is referred to as Chagoma. Acute Chagas disease is subclinical in most individuals. When symptoms are present, it may manifest as a flu-like illness which can last several weeks. Rarely, acute Chagas can result in encephalitis and myocarditis, which can be fatal.

Figure 2.

Romaña’s sign in child with right eye swelling. (Courtesy of CDC’s image library.)

What You should be alert for in the history

Most of the morbitity and mortality due to Chagas disease is due to the chronic phase of the illness. According to World Health Organization (WHO) estimates, there are approximately 10 million people with chronic infection. About 20-30% of infected persons develop chronic disease. Chronic Chagas disease should be suspected in any patient with a history of potential exposure such as living or traveling to endemic areas and who presents with manifestations such as idiopathic cardiomyopathy, arrhythmias, esophageal dysmotility, or megacolon.

Characteristic findings on physical examination

The clinical characteristics of chronic Chagas disease relate to the organs affected. Individuals with cardiomyopathy may present with a history of heart failure or arrhythmias. An EKG may show conduction abnormalities and/or arrhythmias. Echocardiography may show left and/or right ventricular dilation or hypokinesis. Individuals with gastrointestinal (GI) involvement may present with difficulty swallowing, abdominal pain, or history of constipation. Barium swallow may show esophageal dysmotility, achalasia, or megaesophagus. Barium enema will show megacolon. Atypical presentations can be seen in immunocompromised persons such as those with HIV infection and who have undergone organ transplantation.

Diagnosis confirmation

The diagnosis of Chagas can be made during the acute phase of the disease by performing a Giemsa-stained thick or thin blood smear and looking for the trypomastigotes. The latter are more common during the acute phase of the infection but are rarely seen during the chronic phase. The most reliable method of diagnosis is by serology. Several tests have been developed but any single test lacks sensitivity and specificity. Therefore, both an ELISA and indirect fluorescent antibody (IFA) tests are are available through the CDC.

Who is at Risk for Developing this Disease?

The disease is endemic in areas of Mexico, and throughout Central and South America. Transmission takes place in rural areas where sylvatic areas have been cleared to give way to human habitat. Infection usually occurs by the bite of triatomine blood-sucking insect vectors that typically feed on areas of the face such as the conjunctiva and thus are frequently referred to as the kissing bug. They tend to reside in crevices of house walls constructed of mud or in thatched roofs.

The vector and the parasite are also endemic in the southern United States but infection of humans is rare, perhaps due to living conditions not being conducive to vector habitation, low transmission capacity of the vectors, or low infectivity of the local parasite strains. Other less frequent means of transmission include blood transfusions, congenital mother-to-infant, organ transplantation, and ingestion of contaminated food. Infected humans as well as a variety of animals serve as reservoirs for infection of the vector.

What is the Cause of the Disease?

Etiology

The disease, the vector, and its clinical features were first described by the Brazilian physician Carlos Chagas (Figure 3). Chagas disease is caused by the parasite Trypanosoma cruzi transmitted by triatomine vectors of the subfamily Reduviidae.

Figure 3.

Pathophysiology

Trypomastigotes (Figure 4), the motile forms of the parasite, invade muscle and nerve tissues of organs such as the heart and the gastrointestinal tract, causing conduction abnormalities and myopathy leading to dilatation and contractile dysfunction.

Figure 4.

Systemic Implications and Complications

Rarely, acute Chagas disease can result in encephalitis and myocarditis which can be fatal.

The most important systemic manifestions of chronic Chagas disease are cardiac (cardiomyopathy presenting with a history of heart failure or arrhythmias) and GI (presenting with difficulty swallowing, abdominal pain, or history of constipation due to any combination of esophageal dysmotility, achalasia, megaesophagus or megacolon).

Treatment Options

Benznidazole and nifurtimox are the drugs available for treatment. Neither one is licensed in the US and both are available only from the CDC Division of Parasitic Diseases Public (Tel 770-488-7775; email: ncidpdbpi@cdc.gov) or the CDC Drug Service (Tel 404-639-3670) under investigational protocols.

Both drugs have significant side effects. Benznidazole is frequently associated with rashes secondary to photosensitization. In some cases severe exfoliative dermatitis can occur in which case the drug should be discontinued immediately. In addition, peripheral neuropathy can occur late in the course of treatment. Nifurtimox frequently causes GI symptoms including anorexia, nausea, vomiting, and abdominal pain. Peripheral neuropathy can also occur late in the course of treatment.

Due to the risk of bone marrow suppression and hepatitis with both drugs it is recommended that complete blood count and liver enzymes be obtained prior to and periodically during treatment. Benznidazole is considered first line due to its more acceptable side effect profile. The dose regimens are listed in Table I.

Table I.

Drug

Age Group

Dosage and Duration

Benznidazole

< 12 years old

10mg/kg per day orally in 2 divided doses for 60 days

Benznidazole

12 years or older

5-7mg/kg per day orally in 2 divided doses for 60 days

Nifurtimox

< 10 years of age

15-20mg/kg per day orally in 3 or 4 divided doses for 90 days

Nifurtimox

11-16 years of age

12.5-15mg/kg per day orally in 3 or 4 divided doses for 90 days

Nifurtimox

17 years and older

8-10mg/kg per day orally in 3 or 4 divided doses for 90 days

Optimal Therapeutic Approach for this Disease

All individuals with acute infection should be treated. The success rate is better for treatment of acute infection than of chronic infection. In chronically infected individuals, the objective of therapy is to prevent cardiomyopathy which is the main cause of mortality. Treatment is recommended for chronically infected individuals of up to 50 years who do not have advanced cardiomyopathy.

A recent nonrandomized, nonblinded study of benznidazole verus no treatment in patients 30 to 50 years showed decreased progression to cardiomyopathy. It is unclear whether patients with cardiomyopathy benefit from therapy. The answer to this question will have to await the results of an ongoing trial due out in 2012. In the meantime, for treatment of individuals older than 50 the benefits of therapy should be weighed against the risk of side effects.

Patient Management

Patients with advanced Chagas cardiomyopathy or GI complications should be managed in accordance to established guidelines for the conditions. Therefore, patients with arrhythmias should be managed with antiarrythmic agents and if necessary implantable defibrillators. In addition, consideration should be given to cardiac transplantation. In patients with megaesophagus or megacolon, consideration for surgical correction should be given.

Unusual Clinical Scenarios to Consider in Patient Management

Atypical presentations can be seen in immunocompromised persons, such as those with HIV infection and who have undergone organ transplantation. For example, in immunocompromised hosts central nervous system manifestations can occur frequently and include meningoencephalitis or mass lesions.

Bern, C, Montgomery, SP, Herwaldt, BL. “sEvaluation and treatment of chagas disease in the United States: a systematic review”. JAMA. vol. 298. 2007. pp. 2171-81. (This is an excellent general review of the evaluation and treatment of patients with Chagas disease.)